RNA splicing dynamics in CD8 T cells uncovers isoforms that impact T cell-mediated cancer immunotherapy

Authors: Shay Tzaban, Priyanga Appasamy, Elad Zisman, Shiri Klein, Reyut Lewis, Houlin Yu, Akanksha Khorgade, Marc A. Schwartz, Moshe Sade-Feldman, Thomas Eisenhaure, Oren Parnas, Aron Popovtzer, Cyrille Cohen, Eric Shifrut, Aziz M. Al’Khafaji, Rotem karni, Galit Eisenberg, Nir Hacohen, Michal Lotem

This study shows the power of combining HiFi long-read sequencing with single-cell resolution to map isoform usage in human CD8⁺ T cells. By capturing dynamic splicing programs that short-read methods often miss, the team not only redefined T cell states, but also uncovered novel immune checkpoints with therapeutic potential. This work lays the foundation for isoform-selective immunotherapies that are anchored in discovery, validated in vivo, and guided by a generalizable single-cell framework.

Journal: bioRxiv
DOI: 10.1101/2025.09.07.674706
Year: 2025

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